1. Field of the Invention
The invention relates to a polymer, and more specifically to a biocompatible and biodegradable block copolymer and a nanoparticle comprising the same.
2. Description of the Related Art
To improve curative effects and reduce side effects, an optimal drug delivery carrier capable of precisely targeting tumor cells and producing high drug concentration around the focus is required. Such carrier materials must be biocompatible, biodegradable, and undetectable by the immune system to avoid macrophage attack. Common carrier materials comprise block copolymers. Some, however, lack biodegradability, long term stability, and are detectable to immune cells circulating in the blood.
Sugiyama provides a zwitterionic copolymer comprising a hydrophilic chain of 2-(methacryloyloxy)ethyl phosphorylcholine (MPC) and a hydrophobic chain ends of cholesteryl with critical micelle concentration (CMC) of 2.5×10−4-2.7×10−5 wt % recited in Journal of Polymer Science Part A: Polymer Chemistry (2003) 1992-2000. Such material forms a complex with cholesterol molecules in condensed layer morphology with a 3.52 nm interval therebetween. This copolymer provides hemocompatibility and encapsulates water insoluble drugs by hydrophobic cholesterol groups attached on the polymer chains. The material, however, lacks biodegradability.
Stenzel provides a zwitterionic block copolymer comprising poly(2-acryloyloxyethyl phosphorylcholine) and poly(butyl acrylate) with biocompatibility formed by reversible addition fragmentation transfer (RAFT) recited in Macromolecular Bioscience (2004) 445-453. The nanoparticle formed in water and methanol binary solvent thereby has a diameter of about 40-160 nm. This copolymer, however, also lacks biodegradability.
Nakabayashi provides a biodegradable poly(L-lactic acid) (PLLA) material comprising phosphorylcholine such as L-α-glycerophosphorylcholine (LGPC) recited in Journal of Biomedical Materials Research part A (2003) 164-169. Various molecular weight PLLA materials can be polymerized using LGPC as an initiator. According to a blood cell experiment, as the phosphorylcholine content of PLLA increases, blood-cell adsorption decreases. Thais material, however, lacks micelle characteristics.
Oishi provides a novel zwitterionic poly(fumaramate) material comprising phosphorylcholine with CMC of about 1.7×10−3-1.0×10−3 M recited in Polymer (1997) 3109-3115. Conducting isopropyl and methyl groups to fumaramate alters the CMC. According to a bovine serum albumin adsorption experiment, as the phosphorylcholine content of poly(fumaramate) increases, bovine serum albumin adsorption is reduced.
Sommerdijk provides a polystyrene material comprising tetra(ethylene glycol) and phosphorylcholine bonded to its side chain with biocompatibility recited in Journal of Polymer Science Part A: Polymer Chemistry (2001) 468-474. According to a protein adsorption experiment and in vitro human dermal fibroblast culture, only polystyrene material containing tetra(ethylene glycol) and phosphorylcholine can reduce protein adsorption and fibroblast growth, as compared with polystyrene bonded with tetra(ethylene glycol) or phosphorylcholine alone.
Langer provides a biodegradable injection-type nanoparticle comprising diblock (AB) or triblock (ABC) copolymer disclosed in U.S. Pat. Nos. 5,543,158 and 6,007,845. A is a hydrophilic chain such as poly(alkylene glycol), B is a hydrophobic chain such as PLGA, and C is a bioactive substance such as antibody. The particle can target cells or organs by the bioactive substance bonded thereto. These applications, however, fail to disclose that AB or ABC provide invisibility to biorecognition.
Kim provides a biodegradable drug-contained micelle comprising diblock (BA) or triblock (ABA or BAB) copolymer with a preferable molecular weight of about 1430-6000 and a hydrophilic chain ratio of 50-70 wt % disclosed in U.S. Pat. No. 6,322,805. A is a biodegradable hydrophobic chain and B is a hydrophilic chain such as PEG. Drugs such as paclitaxel are physically encapsulated. The application, however, fails to disclose an ABC-type triblock copolymer.
Marchant provides an anti-thrombosis triblock copolymer comprising a hydrophobic biodegradable polymer and a hydrophilic polysaccharide chain such as dextran or heparin disclosed in U.S. Pat. No. 5,741,852.
Ishihara provides a method for preparing a phosphorylcholine-contained polymer in aqueous phase disclosed in U.S. Pat. No. 6,204,324. Adding initiator in aqueous medium polymerizes polymerizable monomers, phosphorylcholine. A separation film, containing impurity of less than 2000 ppm, then purifies the results.